<p>Lung cancer is frequently treated with paclitaxel in combination with several other agents; however, paclitaxel treatment is often ineffective or limited by treatment-related toxicities. Heritable variants in genes associated with absorption, distribution, metabolism, and elimination may predict paclitaxel clinical outcome and toxicity. We designed a prospective multi-institutional study that recruited 546 patients receiving therapy with a 5-year follow up. All patients were genotyped using the Drug Metabolizing Enzymes and Transporters (DMET) platform, which ascertains 1931 genotypes in 235 genes. Genotypes were compared to the progression-free survival of paclitaxel therapy and clinically-significant paclitaxel toxicities. Seven genetic variants were associated with paclitaxel PFS (in <a href="https://www.ncbi.nlm.nih.gov/gene/8647">ABCB11</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/8714">ABCC3</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/9619">ABCG1</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/1582">CYP8B1</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/2908">NR3C1</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/388714">FMO6P</a>, and <a href="https://www.ncbi.nlm.nih.gov/gene/2947">GSTM3</a>), whereas four genetic variants (in <a href="https://www.ncbi.nlm.nih.gov/gene/79001">VKORC1</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/9389">SLC22A14</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/2939">GSTA2</a>, and <a href="https://www.ncbi.nlm.nih.gov/gene/1633">DCK</a>) were associated with paclitaxel toxicities. The present SNPs have limited clinical utility but suggest that certain genes are related to important paclitaxel pathways in lung cancer.</p>

Lung Cancer Pharmacogenomics (LUPG)